Pregnenolone sulfate (hereinafter referred to as “PS”) is a sulfate ester of pregnenolone, which is a steroid hormone generated by cholesterol metabolism. It is known that pregnenolone is further metabolized to generate 17-hydroxypregnenolone or progesterone (non-patent references 1 and 2). PS is generated in the adrenal gland and brain. It is considered that PS generated in the brain acts on only functions of the center of the brain. Such a central nervous system-acting steroid hormone is called a neurosteroid (non-patent reference 3).
The hippocampus is known as an area associated with memory and learning in the brain, and it is known that cytochrome P450scc, an enzyme associated with PS synthesis, exists in neurons in the hippocampus (non-patent reference 4). Further, it is known that cytochrome P450scc exists in intracellular mitochondria, and that PS is generated from cholesterol transported into mitochondria. Furthermore, it is known that the transport of cholesterol into mitochondria is triggered by a calcium influx into cells (non-patent reference 3). Therefore, the calcium influx into cells acts as a trigger of PS synthesis.
To reveal a PS function in the central nervous system, an amount of PS contained in the hippocampus was measured, and as a result, it was found that the concentration of PS is reduced with aging. Further, it was found that the memory and learning ability are reduced in correlation with the PS concentration (non-patent reference 5), and PS is thus considered to be involved in memory and learning. The effects of PS on memory and learning were analyzed closely and carefully, and it was found that PS causes an increase of acetylcholine, a neurotransmitter released from the synaptic terminal, a promotion of frequency in the hippocampal spike, and long term potentiation (LTP), using hippocampal slices (non-patent references 3, 6, and 7). These results show an enhancement of neurotransmission by PS, and thus it was found that PS is involved in memory and learning via the promotion of neurotransmission (non-patent reference 3).
Actually, when PS was administered to aged rats exhibiting a decreased memory and learning ability, the memory and learning ability were improved (non-patent reference 5).
As described above, PS is deeply involved in the mechanism of memory and learning, and a reduced amount of PS produced with aging promotes a reduction in the memory and learning ability, and as a result, dementia develops.
Since the memory and learning ability are improved by an administration of PS, an activity of antidementia can be expected by administering PS to a patient suffering from dementia with aging or enhancing the mechanism of PS.
However, PS has a low transferability into the brain, and thus, it is difficult to use PS per se as an antidementia agent. In addition, a molecule directly targeted by PS is unknown, and it is unknown how the above-described increased hippocampal LTP and increased release of the neurotransmitter are triggered. There is a report in which the existence of an unknown target molecule capable of improving the memory and learning by a direct action of PS is suggested (non-patent reference 3).
A human novel melastatin-like protein is encoded by a human gene similar to a Melastatin gene belonging to a TRPM (Transient Receptor Potential Melastatin) channel family. The sequence of the gene encoding the human novel melastatin-like protein is known, but functions of the protein encoded by the gene, particularly functions in a living body, are unknown (patent reference 1). The sequence of a human TRICH (transporters and ion channels) is known (patent reference 2), and it is described in patent reference 2 that the human TRICH plays a role in transports, the nervous system, muscles, immunity, or cell-proliferation-related diseases. However, experimental supports therefor are not disclosed in patent reference 2, and functions of the human TRICH in a living body are unknown.    (non-patent reference 1) Nippon Rinsho, 1999, vol. 57, p. 162-165    (non-patent reference 2) Nippon Rinsho, 1999, vol. 57, p. 166-169    (non-patent reference 3) Seibutsu Butsuri, 2001, vol. 41, p. 290-294    (non-patent reference 4) Endocrinology, (U.S.A.), 2001, vol. 142, p. 3578-3589    (non-patent reference 5) Proceedings of the National Academy of Sciences of the United States of America, (U.S.A.), 1997, vol. 94, p. 14865-14870    (non-patent reference 6) Epilepsy Research, (Netherlands), 1999, vol. 33, p. 23-29    (non-patent reference 7) Brain Research, (U.S.A.), 2002, vol. 951, p. 237-242    (patent reference 1) International Publication No. WO01/32870    (patent reference 2) International Publication No. W002/77237